Cell communication Flashcards
examples of unicellular communication
quorum sensing in bacteria
- release and response to chemical signals
mating in budding yeast
- signaling b/w yeast cells prepares them to mate
aggregation of ameboid cells
- signalling between dictyostelium cells draws them together
two main ways of receiving a signal
- cell-surface receptors
- for hydrophilic signal molecules - intracellular receptors
- for hydrophobic molecules
- has to pass through the membrane of the target cell
contact-dependent signaling
signals retained on the cell surface
- faster
pararcrine signaling
- signals released from the cell but act locally
restricted by
- internalization by neighbouring cells
- signal instability or destruction by extracellular enzymes
- binding to extracellular matrix molecules
synaptic signaling
neuron reaches a long distance then communicates
- neurons extend acons to contact distant target cells
- the released signaling molecules act locally at target
endocrine signaling
endocrine cells secrete hormones into the bloodstream for long-range distribution
- diffusion out of blood into target cell
signal transduction
the conversion of extracellular signals into intracellular signals
effector
downstream molecule in a signal transduction pathway
- upstream molecules have their effects on them
signal transduction pathway
extracellular signal molecule –> receptor protein –> intracellular signaling proteins –> effector proteins
effector proteins (3)
- metabolic enzyme
- gene regulatory protein
- cytoskeletal protein
second messengers
small intracellular signaling molecules
- made in large numbers and diffuse through cytoplasm or plasma membrane
- bind and alter effector molecules
signaling by phsophorylation
for serine/threonine kinases and tyrosine kinases
- phosphorylation, powered by ATP hydrolysis turns ON
- dephosphorylation turns OFF
signaling by GTP binidng
- large trimeric and small monomeric type proteins
- have low GTPase activity
- GTP binding (GDP –> GTP) turns ON
- GTP hydrolysis (regulated by GAP) turns OFF
GAPs
GTPase activating proteins
- increase the GTP hydrolysis
GEFs
Guanine nucleotide exchange factors
- promote the exchange of GDP for GTP
examples of signaling pathways
- SH2 and PTB domains bind phosphotyrosine containing sequences
- PH domains bind phosphoinositides
- SH3 domains bind proline-rich sequences
synaptic signaling specificity
neurons make connections with specific target cells
- all based on location
- the same neurotransmitter can be used
endocrine signaling specificity
different molecules are released and target cells express specific receptors to respond to specific molecules
what prevents an upstream signal from activating all of the pathways?
the formation of local complexes helps insulate pathways from each other
- must be activated by an activated receptor
coincidence detectors
only activate downstream signals when two upstream signals are both detected
- pathway is activated
- protein kinase phosphorylates y, each specific to one side of y
- downstream signals are only activated if y is phosphorylated on both sides
what determines the response speed to a signal
it varies depending on the cellular machinery involved
effects of positive feedback
- enhancing the response
- strong enough feedback can be self-sustaining
- bistable systems can stably exist in on or off states
effects of negative feedback
- if it occurs quickly, signal is suppressed
- allows cells to respond to changes in upstream signals and a wider range of signal strengths
- if it occurs slowly, the system can oscillate
NO as a signaling molecule
- made by deamination of arginine by NO synthases
- acts locally
- affects smooth muscle and other target cells
- rapid diffusion of NO can cause relaxation of smooth muscle cells
steroid hormones
- made from cholesterol
- affect sexual characteristics and metabolism
thyroid hormones
- made from tyrosine
- increase metabolic rate
retinoids
- made from vitamin A
- regulate development
vitamin D
affects metabolism
nuclear receptor superfamily
- contain binding sites for a small hydrophobic molecule as well as for DNA
- 48 in the human genome
- more than half only identified based on sequence analysis
ligand binding and conformation
- binding to a ligand induces conformation and release of inhibitors
- DNA binding and downstream transcription promoted
ion channel properties
- narrow selective pores
- open and close rapidly
- transport is passive (based on electrochemical gradients and ion diffusion)
different types of ion channels
- voltage gated
- ligand gated (intracellular and extracellular)
- mechanically gated
ion channel functions
- electrical excitability of muscle cells
- electrical signaling in the nervous system
- leaf closure responses in plants
- signal the single-celled paramecium to reverse its movement upon collision
nerve impulses
- synaptic vesicles release neurotransmitters through exocytosis
- these bind to and open ligand gated channels
- channels allow ion passage into the target cell to create another nerve impulse or a different effect
GPCR
G-protein coupled receptors
- 7 pass transmembrane proteins
- activated by proteins, small molecules, and light
- more than 700 in humans
GPCR signaling
- signaling done via a membrane associated trimeric GTP-binding protein
- functions as a GEF to change GDP –> GTP on the alpha subunit
- a subunit goes through a conformational change and induces release of other subunits
- subunits bind to downstream effectors
- turned off by a regulator of G protein signaling (RGS) which acts as a GAP
cAMP and its pathway
- synthesized from ATP by adenylyl cyclase
- destroyed by cAMP phosphodiesterase
- signal is transduced by increasing adenylyl cyclase activity above a constant background of phosphodiesterase activity
- cAMP activates PKA which phosphorylates CREB to activate transcription
- release of separate molecules forms a tetramer
GPCR signaling via calcium
- signal molecule activates GPCR
- Gq is acivated by GTP
- activated phospholipase C-b causes release of IP3
- diacylglycerol is left behind on the membrane
- IP3 diffuses through cytoplasm amd activate IP3 gates
- Ca2+ released and activate PKC
enzyme-coupled receptors
- receptor tyrosine kinases
- receptor serine/threonine kinases
- histidine-kinase-associated receptors
signaling by receptor tyrosine kinase
- ligand binding dimerizes the receptor
- kinase domains brought together and phosphorylate each other at the same time
- phosphorylation of kinase domains enhances activity
- phosphorylation of other regions creates docking sites to assemble a signaling complex
- recruition of proteins that mediate downstream signaling
what happens when a defective kinase domain is expressed with a normal receptor?
the cell has reduced response to the signal
drosophila and tyrosine kinase
- omnatidia compose of photoreceptor and support cells
- arise from epithelial sheet through sequential differentiation of the photoreceptor cells
- R7 is last to differentiate and needed to detect uV light
Sevenless mutant
- helped discover what was necessary for R7 differentiation
- normal Sev protein shown to be a receptor tyrosine kinase in R7 cells
Bride-of-sevenless (Boss)
ligand for Sev expressed on R8 cells
Drk and Son-of-Sevenless (Sos)
- Drk links Sev to Sos
- Sos is a GEF for Ras
Ras
a molecular switch downstream of receptor tyrosine kinase
- monomeric GTPase
- attached to cytoplasmic face of the plasma membrane by a lipid anchor
- activated by Ras-GEF and inactivated by Ras-GAP
- leads to cell proliferation
Ras and MAP kinase module
- Ras activated MAPKKK
- phosphorylates MAPKK
- phosphorylates MAPK
- phosphorylates effecor proteins
- changes in protein activity and gene expression
receptor serine/threonine kinases
- largest class, 6 major families in plants
- Clv1/Clv2 signals stimulate the development of stems, leaves, and flowers
- ser-thr kinase phosphorylates itself and its neighbour
- protein phosphatase can turn off the signal through dephosphorylation
histidine-kinase-associated receptors
- activate a two component signaling pathway
- used by bacteria, yeast, and plants
- repellent binds to receptor activating CheW
- CheA is activated, phosphorylates itself and transfers the phosphate onto CheY
lateral inhibition by notch signaling
- top cell inhibits notch activation
- both start off with delta and prevent each other’s delta expression
- each cell inhibits its neighbour
- cell with active delta specializes
activating a notch cell
- delta binds to big fragment
- top cell has to endocytose the large one
- mediated by clathrin
- rest of notch is activated down
notch cell pathway
- cleavage at site 1
- transport to plasma membrane
- binding to delta, endocytosis of delta-notch-fragment complex and cleavage at site 2
- cleavage at site 3
- notch tail migrates to nucleus
- protein complex containing notch tail activates gene transcription
- leads to inhibition of delta expression and cell specialization
Sonic hedgehog
- source of morphogen
- Shh spreads and the gradient controls formation of distinct digits
- without it, CI is sequestered in the cytoplasm by a microtubule associated complex
- promotes proteolysis of Ci to a transcriptional repressor
Patched
binding with Hedgehog allows smoothened to transfer to the plasma membrane and release Ci from its inhibitory complex
- difference determined by presence or absence of a cut
